G-quadruplex recognition and remodeling by the FANCJ helicase.
G-quadruplex recognition and remodeling by the FANCJ helicase.
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DOI：
10.1093/nar/gkw574
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发表时间：
2016-10-14
影响因子：
14.9
通讯作者：
Spies M
中科院分区：
文献类型：
--
作者：
Wu CG;Spies M
富含鸟嘌呤的核酸序列可以形成干扰DNA复制、修复和RNA转录的G-四链体（G4）结构。人FANCJ解旋酶通过G4形成DNA区域促进DNA复制，有助于维持基因组完整性。在这里，我们结合单分子和合奏生化分析表明，FANCJ具有G4特异性识别位点。通过这种相互作用，FANCJ靶向含G4的DNA，其中其解旋酶和G4结合活性使得能够进行重复的多轮逐步G4解折叠和重折叠。与其他G4重塑酶相比，FANCJ部分稳定了G-四链体。这将保留REV 1跨损伤DNA合成聚合酶的底物，以从复制停滞的G-四链体中掺入胞嘧啶。负责G-四链体识别的残基也参与与MLH 1错配修复蛋白的相互作用，表明支持复制的FANCJ活性及其参与DNA链间交联修复和/或异源双链体排斥是相互排斥的。我们的研究结果不仅描述了FANCJ识别G-四链体并介导其逐步展开的机制，还解释了FANCJ如何通过富含G的序列在支持DNA修复与促进DNA复制之间进行选择。
Guanine rich nucleic acid sequences can form G-quadruplex (G4) structures that interfere with DNA replication, repair and RNA transcription. The human FANCJ helicase contributes to maintaining genomic integrity by promoting DNA replication through G4-forming DNA regions. Here, we combined single-molecule and ensemble biochemical analysis to show that FANCJ possesses a G4-specific recognition site. Through this interaction, FANCJ targets G4-containing DNA where its helicase and G4-binding activities enable repeated rounds of stepwise G4-unfolding and refolding. In contrast to other G4-remodeling enzymes, FANCJ partially stabilizes the G-quadruplex. This would preserve the substrate for the REV1 translesion DNA synthesis polymerase to incorporate cytosine across from a replication-stalling G-quadruplex. The residues responsible for G-quadruplex recognition also participate in interaction with MLH1 mismatch-repair protein, suggesting that the FANCJ activity supporting replication and its participation in DNA interstrand crosslink repair and/or heteroduplex rejection are mutually exclusive. Our findings not only describe the mechanism by which FANCJ recognizes G-quadruplexes and mediates their stepwise unfolding, but also explain how FANCJ chooses between supporting DNA repair versus promoting DNA replication through G-rich sequences.
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DOI：
10.1038/nrg3296
发表时间：
2012-11
期刊：
Nature reviews. Genetics
影响因子：
--
作者：
通讯作者：
--
影响因子：
14.9
作者：
Johnson J;Okyere R;Joseph A;Musier-Forsyth K;Kankia B
通讯作者：
Kankia B
影响因子：
4.8
作者：
Bain, Fletcher E.;Wu, Colin G.;Spies, Maria
通讯作者：
Spies, Maria
影响因子：
46.9
作者：
Chambers, Vicki S.;Marsico, Giovanni;Balasubramanian, Shankar
通讯作者：
Balasubramanian, Shankar
影响因子：
14.9
作者：
Budhathoki JB;Ray S;Urban V;Janscak P;Yodh JG;Balci H
通讯作者：
Balci H